PROJECT SUMMARY/ABSTRACT Young people aged 10 to 24 years and living with HIV (YPLWH) have high rates of HIV-related morbidity and mortality, particularly in sub-Saharan Africa. Additional research with YPLWH is urgently needed to inform HIV programs and policies, however, there are insufficient ethical guidelines on research with YPLWH in diverse cultural and socioeconomic contexts. The long-term goal of our research is to provide evidence to inform and improve the care of children and YPLWH in Kenya and other resource-limited settings. This proposal will investigate bioethical research gaps in research with YPLWH and provide recommendations to inform ethical guidelines and policies. This work will take place through a long-standing academic partnership between Kenyan and North American universities called the Academic Model Providing Access to Healthcare (AMPATH), where we also maintain community and governmental partnerships. The specific aims for this study are: Aim 1: Explore ethical issues in longitudinal clinical research with YPLWH in Kenya from the perspective of YPLWH, caregivers, and other key informants. Aim 2: Analyze key bioethics guidelines and policies relevant to research with YPLWH in Kenya. To achieve Aim 1, we will conduct in-depth interviews with YPLWH (research experienced and not), caregivers of YPLWH, and a diverse range of stakeholders: community leaders, youth and community advisory boards, healthcare providers, IRB members, researchers, laboratory heads, and government representatives. Interviews will examine ethical issues related to adolescent and young adult participation, as well as the collection, storage and future use of biological samples. To enroll YPLWH and caregivers experienced in research, we will leverage an ongoing parent R01 (R01AI14733301, MPIs: Kantor and Vreeman) that is longitudinally examining viral and drug resistance outcomes for a well- characterized cohort of 499 Kenyan YPLWH for 4 years, including biannual blood specimens. To achieve Aim 2, we will identify global, regional, and Kenyan ethical guidelines and policies relevant to research across key areas: children and YPLWH, people living with HIV, biological sampling and biobanking, and research in resource-limited settings. Qualitative data will be analyzed using a content analysis and framework approach, with an initial coding guide informed deductively by the themes described above and refined inductively. Triangulation will be used to explore convergence, complementarity, and dissonance across data sources and methods. The outcomes of our proposed supplement will guide the ethical conduct of the parent R01 and lead to novel insights on critical ethical issues for research with YPLWH in Kenya and other settings. After completing the aims of this supplement, we will integrate our findings from interviews with YPLWH, caregivers, and key stakeholders and the document analysis to generate concrete recommendations. We will disseminate our findings and recommendations through bioethics-related academic and policy forums and a comprehensive policy brief to be shared with research participants and relevant local and global stakeholders.